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Stephen V Liu

28 Jan, 6 tweets, 6 min read

@OncoAlert

#WCLC20 This poster outlines biomarker work in the phase I study of patritumab deruxtecan (HER3-DXd), a HER3-ADC, focused on patients with #EGFR mutant NSCLC after prior TKI and chemotherapy. Note diversity of EGFR TKI resistance mechanisms in this small sample! #LCSM @OncoAlert

#WCLC20 The efficacy of HER3-DXd in #EGFR mutant NSCLC was seen across various resistance mechanisms and for such a heterogeneous pretreated population, very promising activity. #LCSM

#WCLC20 At baseline, nearly all tumor expressed HER3 independent of when #EGFR TKI was stopped. Some association with expression and efficacy. I always feel this should be a stronger association given how I think ADCs work but maybe I don't know how ADCs work. #LCSM

#WCLC20 These data are consistent with what we see in ctDNA from other studies. Clinical response associated with more rapid clearance of #EGFR mutation in ctDNA. Lack of clearance associated with poorer outcomes. #LCSM

#WCLC20 Shown another way - patients who do not clear ctDNA at week 3 less likely to respond. How far are we from incorporating liquid biopsy as an early pharmacodynamic marker to assure we're on the right track (or alert us that we're not)? I think we're kind of right there...

@HelenaYu923

#WCLC20 Overall, this seems to be an exciting agent and looking forward to seeing its activity in larger trials. Activity across diverse resistance profiles and clearance of ctDNA may be a useful early biomarker. Great work by whole team including Dr. @HelenaYu923 #LCSM @IASLC

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Stephen V Liu

@StephenVLiu

29 Jan

@JSabari

#WCLC20 CHRYSALIS trial results with amivantamab in #EGFRex20 NSCLC post-platinum based chemotherapy presented by @JSabari. Amivantamab has FDA breakthrough designation for this indication. @IASLC #LCSM @OncoAlert

#WCLC20 Amivantamab is an EGFR-MET bispecific antibody given intravenously weekly x 1 month then q2w. This is a single arm phase II for patients with #EGFRex20 mutant NSCLC after prior chemotherapy. #LCSM

#WCLC20 Amivantamab was reasonably well tolerated. G3 TEAE in 35% but treatment-related rate only 16%. Drug related AE leading to discontinuation only 4%. Mostly G1-2 adverse events including rash, paronychia. #LCSM

Read 4 tweets

Stephen V Liu

@StephenVLiu

29 Jan

@IASLC

#WCLC20 Dr. Nakagawa presents results from the DESTINY-Lung01 trial of trastuzumab deruxtecan (T-DXd, Enhertu). T-DXd is a HER2 antibody-drug conjugate (ADC). #LCSM @IASLC @OncoAlert

#WCLC20 This study had two cohorts. Here, we focus on Cohort 1 (HER2-overexpressing = IHC3+ or IHC2+). Primary response rate was ORR. #LCSM

@NCCN

#WCLC20 As a reminder, we saw results from Cohort 2 (HER2-mutant) at #ASCO20 where they reported an ORR of 61.9% with mPFS 14.0m, which led to the inclusion of T-DXd in the @NCCN guidelines for #HER2 mutant NSCLC. #LCSM

Read 8 tweets

Stephen V Liu

@StephenVLiu

29 Jan

@Jbauml

#WCLC20 Highly anticipated results of oral TKI mobocertinib (TAK-788) in #EGFRex20 mutant NSCLC after prior platinum based chemotherapy. Huge unmet need and as @Jbauml reported at this meeting, likely underdiagnosed. #LCSM @IASLC @OncoAlert

@IASLC

#WCLC20 Cohort being discussed here is #EGFR exon 20 insertion NSCLC after prior platinum therapy and the EXCLAIM extension cohort. Many patients also had prior TKI therapy and prior immunotherapy. @IASLC

#WCLC20 Here are the topline results. RR 23-26% by IRC, RR 32-35% by investigator, DOR by IRC was 17.5m (!) and mPFS 7.3m -- for #EGFRex20, no clear standard. Mobocertinib certainly has some activity here. #LCSM

Read 6 tweets

Stephen V Liu

@StephenVLiu

29 Jan

@IASLC

#WCLC20 Results from the phase III non-inferiority J-AXEL study of salvage nab-paclitaxel vs docetaxel in NSCLC. Large study (n>500) with a 1:1 randomization. #LCSM @IASLC @OncoAlert

#WCLC20 Positive study! Shows non-inferiority in OS with nab-paclitaxel over docetaxel (median 16.2m vs 13.6m). PFS favors nab-pac (HR 0.76). #LCSM

#WCLC20 RR favors nab-paclitaxel (30% vs 15%) and in this study, unlike the registrational trial, no real difference between squamous and non-squamous (both 30%, both better than docetaxel). #LCSM

Read 4 tweets

Stephen V Liu

@StephenVLiu

29 Jan

@HelenaYu923

#WCLC20 Excited about this one: phase I results of the HER3 ADC patritumab deruxtecan (HER3-DXd; U3-1402) in #EGFR mutant #NSCLC presented by @HelenaYu923 #LCSM @IASLC @OncoAlert

@IASLC

#WCLC20 Presentation here is on the combined dose escalation and expansion at the 5.6 mg/kg dose with #EGFR mutant NSCLC. Includes 56 evaluable patients. Median f/u 5 months. #LCSM @IASLC

#WCLC20 Fairly heavily pretreated population with both TKI and chemotherapy and many with IO as well. Biopsy required for HER3 expression (violin plot on right) and nearly all were HER3 positive. #LCSM

Read 6 tweets

Stephen V Liu

@StephenVLiu

29 Jan

@AlexSpiraMDPhD

#WCLC20 Results from phase I study of the TROP2 ADC datopotamab deruxtecan (Dato-DXd; DS-1062) in NSCLC by @AlexSpiraMDPhD #LCSM @IASLC @OncoAlert

#WCLC20 This ADC includes an anti-TROP2 IgG1 and a topo-1 inhibitor payload. Phase 1 design shown here. Mostly non-squamous, included some #EGFR+, heavily pretreated including many with CNS metastases. Less intensity at higher 8mg dose, as one would expect. #LCSM

#WCLC20 Safety shown here and manageable but I would say still notable, especially at 8mg (G3+ AEs 34%) including ILD noted in 8% (but 3 grade 5 cases in the 8mg/kg cohort). #LCSM

Read 5 tweets

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